Murine retroviruses differing in ability to induce brain disease have been compared to elucidate the mechanisms leading to brain dysfunction and death. Clinical disease is preceded by increased expression of several cytokines and chemokines suggesting that these changes may be involved in the induction of disease. Recent results have using knock-out mice lacking certain chemokine receptors indicates that some receptors are not required for disease whereas others are important in the pathogenesis. Current efforts are aimed at determining which brain cell types are producing these molecules. In a separate series of experiments the immune response to Friend murine leukemia virus was correlated with major histocompatibility genotype, and CD8 T cells were found to exert a helper effect of the response of CD4 T cells to this virus. This effect of CD8 T cells could also be demonstrated by adoptive transfer of cells from vaccine primed animals to non-vaccinated recipients. These mechanisms of immunity to pathogens could provide an additional means for evolutionary selection of major histocompatibility genes.